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Protein

Mothers against decapentaplegic homolog 5

Gene

SMAD5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi65 – 651ZincBy similarity
Metal bindingi110 – 1101ZincBy similarity
Metal bindingi122 – 1221ZincBy similarity
Metal bindingi127 – 1271ZincBy similarity

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. receptor signaling protein activity Source: UniProtKB
  3. RNA polymerase II core promoter sequence-specific DNA binding Source: Ensembl
  4. sequence-specific DNA binding transcription factor activity Source: InterPro
  5. transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: BHF-UCL
  6. ubiquitin protein ligase binding Source: BHF-UCL

GO - Biological processi

  1. BMP signaling pathway Source: UniProtKB
  2. bone development Source: Ensembl
  3. cardiac muscle contraction Source: Ensembl
  4. cartilage development Source: Ensembl
  5. cellular response to BMP stimulus Source: BHF-UCL
  6. cellular response to organic cyclic compound Source: Ensembl
  7. embryonic pattern specification Source: UniProtKB
  8. erythrocyte differentiation Source: Ensembl
  9. germ cell development Source: Ensembl
  10. intracellular signal transduction Source: GOC
  11. Mullerian duct regression Source: Ensembl
  12. osteoblast fate commitment Source: Ensembl
  13. positive regulation of osteoblast differentiation Source: Ensembl
  14. positive regulation of transcription, DNA-templated Source: UniProtKB
  15. positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
  16. protein phosphorylation Source: Ensembl
  17. signal transduction Source: UniProtKB
  18. transcription, DNA-templated Source: UniProtKB-KW
  19. transforming growth factor beta receptor signaling pathway Source: UniProtKB
  20. ureteric bud development Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_12034. Signaling by BMP.
SignaLinkiQ99717.

Names & Taxonomyi

Protein namesi
Recommended name:
Mothers against decapentaplegic homolog 5
Short name:
MAD homolog 5
Short name:
Mothers against DPP homolog 5
Alternative name(s):
JV5-1
SMAD family member 5
Short name:
SMAD 5
Short name:
Smad5
Short name:
hSmad5
Gene namesi
Name:SMAD5
Synonyms:MADH5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:6771. SMAD5.

Subcellular locationi

Cytoplasm. Nucleus
Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: Reactome
  3. integral component of membrane Source: UniProtKB
  4. intracellular Source: UniProtKB
  5. nucleoplasm Source: HPA
  6. nucleus Source: UniProtKB
  7. protein complex Source: MGI
  8. transcription factor complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi419 – 4191G → S: Loss of phosphorylation. 1 Publication

Organism-specific databases

PharmGKBiPA30528.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 465464Mothers against decapentaplegic homolog 5PRO_0000090865Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylthreonine2 Publications
Modified residuei463 – 4631Phosphoserine1 PublicationPROSITE-ProRule annotation
Modified residuei465 – 4651Phosphoserine1 PublicationPROSITE-ProRule annotation

Post-translational modificationi

Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.1 Publication
Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ99717.
PaxDbiQ99717.
PRIDEiQ99717.

PTM databases

PhosphoSiteiQ99717.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiQ99717.
CleanExiHS_SMAD5.
ExpressionAtlasiQ99717. baseline and differential.
GenevestigatoriQ99717.

Organism-specific databases

HPAiHPA058931.

Interactioni

Subunit structurei

May form trimers with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3. Interacts with WWP1.2 Publications

Protein-protein interaction databases

BioGridi110265. 57 interactions.
DIPiDIP-57571N.
IntActiQ99717. 28 interactions.
MINTiMINT-1180224.
STRINGi9606.ENSP00000384803.

Structurei

3D structure databases

ProteinModelPortaliQ99717.
SMRiQ99717. Positions 10-133, 270-453.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 137125MH1PROSITE-ProRule annotationAdd
BLAST
Domaini271 – 465195MH2PROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi40 – 467Poly-Lys

Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated
Contains 1 MH1 (MAD homology 1) domain.PROSITE-ProRule annotation
Contains 1 MH2 (MAD homology 2) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG330956.
GeneTreeiENSGT00760000119091.
HOVERGENiHBG053353.
InParanoidiQ99717.
KOiK16790.
PhylomeDBiQ99717.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProiIPR013790. Dwarfin.
IPR003619. MAD_homology1_Dwarfin-type.
IPR013019. MAD_homology_MH1.
IPR017855. SMAD_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PANTHERiPTHR13703. PTHR13703. 1 hit.
PfamiPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTiSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEiPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99717-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME
60 70 80 90 100
ELEKALSSPG QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS
110 120 130 140 150
HHELKPLDIC EFPFGSKQKE VCINPYHYKR VESPVLPPVL VPRHNEFNPQ
160 170 180 190 200
HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP NNTPFPLSPN SPYPPSPASS
210 220 230 240 250
TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMGQDNSQP MDTSNNMIPQ
260 270 280 290 300
IMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT
310 320 330 340 350
DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD
360 370 380 390 400
SSIFVQSRNC NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF
410 420 430 440 450
EAVYELTKMC TIRMSFVKGW GAEYHRQDVT STPCWIEIHL HGPLQWLDKV
460
LTQMGSPLNP ISSVS
Length:465
Mass (Da):52,258
Last modified:May 1, 1997 - v1
Checksum:i4A1FD7EC7BD06728
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti175 – 1751D → H in AAC50791. (PubMed:8673135)Curated
Sequence conflicti237 – 2371N → P in AAC50791. (PubMed:8673135)Curated
Sequence conflicti293 – 2931S → R in AAC50791. (PubMed:8673135)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U59913 mRNA. Translation: AAC50791.1.
AF010601 mRNA. Translation: AAB66353.1.
AF010607
, AF010602, AF010603, AF010604, AF010605, AF010606 Genomic DNA. Translation: AAB92396.1.
U73825 mRNA. Translation: AAB95090.1.
AF009744
, AF009739, AF009740, AF009741, AF009742, AF009743 Genomic DNA. Translation: AAB82655.1.
AF009678 mRNA. Translation: AAB72180.1.
BC009682 mRNA. Translation: AAH09682.1.
CCDSiCCDS75308.1.
RefSeqiNP_001001419.1. NM_001001419.2.
NP_001001420.1. NM_001001420.2.
NP_005894.3. NM_005903.6.
UniGeneiHs.167700.

Genome annotation databases

EnsembliENST00000545279; ENSP00000441954; ENSG00000113658.
ENST00000545620; ENSP00000446474; ENSG00000113658.
GeneIDi4090.
KEGGihsa:4090.
UCSCiuc003lbj.1. human.

Polymorphism databases

DMDMi13959566.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U59913 mRNA. Translation: AAC50791.1.
AF010601 mRNA. Translation: AAB66353.1.
AF010607
, AF010602, AF010603, AF010604, AF010605, AF010606 Genomic DNA. Translation: AAB92396.1.
U73825 mRNA. Translation: AAB95090.1.
AF009744
, AF009739, AF009740, AF009741, AF009742, AF009743 Genomic DNA. Translation: AAB82655.1.
AF009678 mRNA. Translation: AAB72180.1.
BC009682 mRNA. Translation: AAH09682.1.
CCDSiCCDS75308.1.
RefSeqiNP_001001419.1. NM_001001419.2.
NP_001001420.1. NM_001001420.2.
NP_005894.3. NM_005903.6.
UniGeneiHs.167700.

3D structure databases

ProteinModelPortaliQ99717.
SMRiQ99717. Positions 10-133, 270-453.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110265. 57 interactions.
DIPiDIP-57571N.
IntActiQ99717. 28 interactions.
MINTiMINT-1180224.
STRINGi9606.ENSP00000384803.

PTM databases

PhosphoSiteiQ99717.

Polymorphism databases

DMDMi13959566.

Proteomic databases

MaxQBiQ99717.
PaxDbiQ99717.
PRIDEiQ99717.

Protocols and materials databases

DNASUi4090.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000545279; ENSP00000441954; ENSG00000113658.
ENST00000545620; ENSP00000446474; ENSG00000113658.
GeneIDi4090.
KEGGihsa:4090.
UCSCiuc003lbj.1. human.

Organism-specific databases

CTDi4090.
GeneCardsiGC05P135470.
HGNCiHGNC:6771. SMAD5.
HPAiHPA058931.
MIMi603110. gene.
neXtProtiNX_Q99717.
PharmGKBiPA30528.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG330956.
GeneTreeiENSGT00760000119091.
HOVERGENiHBG053353.
InParanoidiQ99717.
KOiK16790.
PhylomeDBiQ99717.

Enzyme and pathway databases

ReactomeiREACT_12034. Signaling by BMP.
SignaLinkiQ99717.

Miscellaneous databases

ChiTaRSiSMAD5. human.
GeneWikiiMothers_against_decapentaplegic_homolog_5.
GenomeRNAii4090.
NextBioi16034.
PROiQ99717.
SOURCEiSearch...

Gene expression databases

BgeeiQ99717.
CleanExiHS_SMAD5.
ExpressionAtlasiQ99717. baseline and differential.
GenevestigatoriQ99717.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProiIPR013790. Dwarfin.
IPR003619. MAD_homology1_Dwarfin-type.
IPR013019. MAD_homology_MH1.
IPR017855. SMAD_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PANTHERiPTHR13703. PTHR13703. 1 hit.
PfamiPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTiSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEiPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Localization of SMAD5 and its evaluation as a candidate myeloid tumor suppressor."
    Hejlik D.P., Kottickal L.V., Liang H., Fairman J., Davis T., Janecki T., Sexton D., Perry W. III, Tavtigian S.V., Teng D.H., Nagarajan L.
    Cancer Res. 57:3779-3783(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
  3. "Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60."
    Zavadil J., Brezinova J., Svoboda P., Zemanova Z., Michalova K.
    Leukemia 11:1187-1192(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors."
    Gemma A., Hagiwara K., Vincent F., Ke Y., Hancock A.R., Nagashima M., Bennett W.P., Harris C.C.
    Oncogene 16:951-956(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. "Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12."
    Nishimura R., Kato Y., Chen D., Harris S.E., Mundy G.R., Yoneda T.
    J. Biol. Chem. 273:1872-1879(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLY-419.
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Uterus.
  7. Bienvenut W.V., Lempens A., Norman J.C.
    Submitted (OCT-2009) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 2-16; 34-40; 130-158; 283-306 AND 309-319, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Ovarian carcinoma.
  8. Cited for: REVIEW.
  9. "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells."
    Verschueren K., Huylebroeck D.
    Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  10. Cited for: REVIEW.
  11. Cited for: REVIEW.
  12. "Suv39h histone methyltransferases interact with Smads and cooperate in BMP-induced repression."
    Frontelo P., Leader J.E., Yoo N., Potocki A.C., Crawford M., Kulik M., Lechleider R.J.
    Oncogene 23:5242-5251(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SUV39H1 AND SUV39H2.
  13. "The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines."
    Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S., Luo K.
    J. Biol. Chem. 280:15992-16001(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LEMD3.
  14. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
    Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  16. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  17. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463 AND SER-465, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  19. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
    Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
    Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  20. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiSMAD5_HUMAN
AccessioniPrimary (citable) accession number: Q99717
Secondary accession number(s): O14688, Q15798, Q9UQA1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: May 1, 1997
Last modified: February 4, 2015
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.